89797-00-2Relevant articles and documents
A selective process for n-alkylation in competition with o-alkylation: Boric acid, borax, and metaborate as a cheap and effective protecting group applicable for industrial-scale synthetic processes
Bjorsvik, Hans-Rene,Priebe, Hanno,Cervenka, Jan,Aabye, Arne W.,Gulbrandsen, Trygve,Bryde, Arnt Christian
, p. 472 - 478 (2013/09/07)
This paper describes a selective process for the N-alkylation of substrates that contain 1,2-diol groups. The developed approach utilises temporary protection of the diol groups by boric acid, Borax, or metaborate. The introduction of the boron-containing groups into the substrate may provide, in addition to affording the intended protection of the hydroxyl groups that may otherwise act as nucleophilic sites, the advantages of improved solubility of the substrate in water that is used as solvent. Moreover the N-alkylation and the deprotection of the diols are performed in one pot, and the formation of undesired O-alkylated by-products is significantly reduced. The paper gives examples from the synthesis of several X-ray contrast agents used in medical imaging diagnostics: iohexol (Ominipaque, Nycomed Imaging); iopentol (Imagopaque, Nycomed Imaging); iodixanol (Visipaque, Nycomed Imaging); ioversol (Optiray, Mallinckrodt).